Autophagy-Induced HDAC6 Activity During Hypoxia Regulates Mitochondrial Energy Metabolism Through the β-Catenin/COUP-TFII Axis in Hepatocellular Carcinoma Cells

Hypoxia is one of the main driving forces that results in poor outcomes and drug resistance in hepatocellular carcinoma (HCC). As the critical cellular oxygen sensor, mitochondria respond to hypoxic stress by sending retrograde signals to the nucleus that initiate adaptive metabolic responses and ma...

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Autores principales:	Xiaoyu Yan, Xianzhi Qu, Buhan Liu, Yuanxin Zhao, Long Xu, Sihang Yu, Jian Wang, Liying Wang, Jing Su
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	hypoxia HDAC6 β-catenin hepatocellular carcinoma autophagy mitochondrial energy metabolism Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/f5fd648f117d41d0af50eea1968f2349
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spelling	oai:doaj.org-article:f5fd648f117d41d0af50eea1968f23492021-11-11T10:39:14ZAutophagy-Induced HDAC6 Activity During Hypoxia Regulates Mitochondrial Energy Metabolism Through the β-Catenin/COUP-TFII Axis in Hepatocellular Carcinoma Cells2234-943X10.3389/fonc.2021.742460https://doaj.org/article/f5fd648f117d41d0af50eea1968f23492021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.742460/fullhttps://doaj.org/toc/2234-943XHypoxia is one of the main driving forces that results in poor outcomes and drug resistance in hepatocellular carcinoma (HCC). As the critical cellular oxygen sensor, mitochondria respond to hypoxic stress by sending retrograde signals to the nucleus that initiate adaptive metabolic responses and maintain the survival of HCC cells. Increasing evidence suggested autophagy contributes to sustain mitochondrial metabolic and quality control. Understanding how mitochondria communicate with the nucleus and alter transcription may provide promising targets for HCC treatment. In this study, we found mitochondrial undergoes selective degradation by autophagy under hypoxia. Furthermore, autophagy-activated HDAC6 not only promoted the nuclear translocation of β-catenin but also increased the affinity of β-catenin to the transcription repressor chicken ovalbumin upstream promoter-transcription factor 2 (COUP-TF II), which suppressed mitochondrial oxidative phosphorylation-related genes transcription. Our data showed that autophagy served as a critical mediator of integrating mitochondrial energy metabolism and nuclear transcription. HDAC6 may be a potential target for reducing the survival of HCC cells by interrupting mitochondria-nucleus crosstalk.Xiaoyu YanXianzhi QuBuhan LiuYuanxin ZhaoLong XuSihang YuJian WangLiying WangJing SuFrontiers Media S.A.articlehypoxiaHDAC6β-cateninhepatocellular carcinomaautophagymitochondrial energy metabolismNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	hypoxia HDAC6 β-catenin hepatocellular carcinoma autophagy mitochondrial energy metabolism Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	hypoxia HDAC6 β-catenin hepatocellular carcinoma autophagy mitochondrial energy metabolism Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Xiaoyu Yan Xianzhi Qu Buhan Liu Yuanxin Zhao Long Xu Sihang Yu Jian Wang Liying Wang Jing Su Autophagy-Induced HDAC6 Activity During Hypoxia Regulates Mitochondrial Energy Metabolism Through the β-Catenin/COUP-TFII Axis in Hepatocellular Carcinoma Cells
description	Hypoxia is one of the main driving forces that results in poor outcomes and drug resistance in hepatocellular carcinoma (HCC). As the critical cellular oxygen sensor, mitochondria respond to hypoxic stress by sending retrograde signals to the nucleus that initiate adaptive metabolic responses and maintain the survival of HCC cells. Increasing evidence suggested autophagy contributes to sustain mitochondrial metabolic and quality control. Understanding how mitochondria communicate with the nucleus and alter transcription may provide promising targets for HCC treatment. In this study, we found mitochondrial undergoes selective degradation by autophagy under hypoxia. Furthermore, autophagy-activated HDAC6 not only promoted the nuclear translocation of β-catenin but also increased the affinity of β-catenin to the transcription repressor chicken ovalbumin upstream promoter-transcription factor 2 (COUP-TF II), which suppressed mitochondrial oxidative phosphorylation-related genes transcription. Our data showed that autophagy served as a critical mediator of integrating mitochondrial energy metabolism and nuclear transcription. HDAC6 may be a potential target for reducing the survival of HCC cells by interrupting mitochondria-nucleus crosstalk.
format	article
author	Xiaoyu Yan Xianzhi Qu Buhan Liu Yuanxin Zhao Long Xu Sihang Yu Jian Wang Liying Wang Jing Su
author_facet	Xiaoyu Yan Xianzhi Qu Buhan Liu Yuanxin Zhao Long Xu Sihang Yu Jian Wang Liying Wang Jing Su
author_sort	Xiaoyu Yan
title	Autophagy-Induced HDAC6 Activity During Hypoxia Regulates Mitochondrial Energy Metabolism Through the β-Catenin/COUP-TFII Axis in Hepatocellular Carcinoma Cells
title_short	Autophagy-Induced HDAC6 Activity During Hypoxia Regulates Mitochondrial Energy Metabolism Through the β-Catenin/COUP-TFII Axis in Hepatocellular Carcinoma Cells
title_full	Autophagy-Induced HDAC6 Activity During Hypoxia Regulates Mitochondrial Energy Metabolism Through the β-Catenin/COUP-TFII Axis in Hepatocellular Carcinoma Cells
title_fullStr	Autophagy-Induced HDAC6 Activity During Hypoxia Regulates Mitochondrial Energy Metabolism Through the β-Catenin/COUP-TFII Axis in Hepatocellular Carcinoma Cells
title_full_unstemmed	Autophagy-Induced HDAC6 Activity During Hypoxia Regulates Mitochondrial Energy Metabolism Through the β-Catenin/COUP-TFII Axis in Hepatocellular Carcinoma Cells
title_sort	autophagy-induced hdac6 activity during hypoxia regulates mitochondrial energy metabolism through the β-catenin/coup-tfii axis in hepatocellular carcinoma cells
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/f5fd648f117d41d0af50eea1968f2349
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Autophagy-Induced HDAC6 Activity During Hypoxia Regulates Mitochondrial Energy Metabolism Through the β-Catenin/COUP-TFII Axis in Hepatocellular Carcinoma Cells

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